CAS 70476-82-3|Mitoxantrone 2HCl
Introduction：Basic information about CAS 70476-82-3|Mitoxantrone 2HCl, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
| Common Name | Mitoxantrone 2HCl | ||
|---|---|---|---|
| CAS Number | 70476-82-3 | Molecular Weight | 517.403 |
| Density | / | Boiling Point | 805.7ºC at 760 mmHg |
| Molecular Formula | C22H30Cl2N4O6 | Melting Point | 203-205ºC |
| MSDS | ChineseUSA | Flash Point | 441.1ºC |
| Symbol | GHS08 | Signal Word | Danger |
Names
| Name | mitoxantrone dihydrochloride |
|---|---|
| Synonym | More Synonyms |
Mitoxantrone 2HCl BiologicalActivity
| Description | Mitoxantrone dihydrochloride is a topoisomerase II inhibitor; also inhibits protein kinase C (PKC) activity with an IC50 of 8.5 μM. |
|---|---|
| Related Catalog | Signaling Pathways >>Epigenetics >>PKCSignaling Pathways >>TGF-beta/Smad >>PKCResearch Areas >>Cancer |
| Target | PKC:8.5 μM (IC50) Topoisomerase II |
| In Vitro | Mitoxantrone inhibits PKC in a competitive manner with respect to histone H1, and its Ki value is 6.3 μM and in a non-competitive manner with respect to phosphatidylserine and ATP[1]. Treatment of B-CLL cells for 48 h with mitoxantrone (0.5 μg/mL) induces a decrease in cell viability. Mitoxantrone induces DNA fragmentation and the proteolytic cleavage of poly(ADP-ribose) polymerase (PARP), demonstrating that the cytotoxic effect of mitoxantrone is due to induction of apoptosis[2]. Mitoxantrone shows cytotoxicity to human breast carcinoma cell lines MDA-MB-231 and MCF-7 with IC50 values of 18 and 196 nM, respectively[3]. |
| In Vivo | Mitoxantrone given IP at the optimal dose (1.6 mg/kg/day; as a free base) produces a statistically significant number of 60-day survivors (curative effect) in mice with IP implanted L1210 leukemia. In SC implanted Lewis lung carcinoma, mitoxantrone and ADM administered IV also shows effective antitumor activities and produces a 60% and a 45% ILS, respectively.[4]. |
| Cell Assay | The human breast carcinoma cell lines MDA-MB-231 and MCF-7 are seeded in standard 96-well plates. One day after seeding, the culture medium is changed and replaced by medium containing different concentration of Mitoxantrone (10-5 to 5 μM) with or without DHA (30 μM) during 7 days. Viability of cells are measured as a whole by the tetrazolium salt assay[3]. |
| Animal Admin | Mice: Mitoxantrone is tested for antitumor activity against experimental tumors in mice and the results are compared with those of seven antitumor antibiotics. The drugs are given IP or IV, in general on days 1, 5, and 9 following tumor inoculation. Mitoxantrone is given IP at the optimal dose (1.6 mg/kg/day; as a free base)[4]. |
| References | [1]. Takeuchi N, et al. Inhibitory effect of mitoxantrone on activity of protein kinase C and growth of HL60 cells. J Biochem. 1992 Dec;112(6):762-7. [2]. Bellosillo B, et al. Mitoxantrone, a topoisomerase II inhibitor, induces apoptosis of B-chronic lymphocytic leukaemia cells. Br J Haematol. 1998 Jan;100(1):142-6. [3]. Venza I, et al. Class II-specific histone deacetylase inhibitors MC1568 and MC1575 suppress IL-8 expression in human melanoma cells. Pigment Cell Melanoma Res. 2013 Mar;26(2):193-204. [4]. Fujimoto S, et al. Antitumor activity of mitoxantrone against murine experimental tumors: comparative analysis against various antitumor antibiotics. Cancer Chemother Pharmacol. 1982;8(2):157-62. |
Chemical & Physical Properties
| Boiling Point | 805.7ºC at 760 mmHg |
|---|---|
| Melting Point | 203-205ºC |
| Molecular Formula | C22H30Cl2N4O6 |
| Molecular Weight | 517.403 |
| Flash Point | 441.1ºC |
| Exact Mass | 516.154236 |
| PSA | 163.18000 |
| LogP | 2.39260 |
| InChIKey | ZAHQPTJLOCWVPG-UHFFFAOYSA-N |
| SMILES | Cl.Cl.O=C1c2c(O)ccc(O)c2C(=O)c2c(NCCNCCO)ccc(NCCNCCO)c21 |
Toxicological Information
CHEMICAL IDENTIFICATION |
ACUTE TOXICITY DATA - TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Intravenous
- SPECIES OBSERVED :
- Human - woman
- DOSE/DURATION :
- 4400 ug/kg/30W-I
- TOXIC EFFECTS :
- Skin and Appendages - nails
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Parenteral
- SPECIES OBSERVED :
- Human - man
- DOSE/DURATION :
- 71 ug/kg/2W-I
- TOXIC EFFECTS :
- Peripheral Nerve and Sensation - flaccid paralysis without anesthesia (usually neuromuscular blockage)
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- 682 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Administration onto the skin
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- 1640 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Intraperitoneal
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- 8 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Subcutaneous
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- 5500 ug/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Intravenous
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- 4800 ug/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Rodent - mouse
- DOSE/DURATION :
- 502 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Intraperitoneal
- SPECIES OBSERVED :
- Rodent - mouse
- DOSE/DURATION :
- 16500 ug/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Subcutaneous
- SPECIES OBSERVED :
- Rodent - mouse
- DOSE/DURATION :
- 19700 ug/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Intravenous
- SPECIES OBSERVED :
- Rodent - mouse
- DOSE/DURATION :
- 9700 ug/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Intraperitoneal
- SPECIES OBSERVED :
- Mammal - dog
- DOSE/DURATION :
- >1200 ug/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Intravenous
- SPECIES OBSERVED :
- Mammal - dog
- DOSE/DURATION :
- 375 ug/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Intravenous
- SPECIES OBSERVED :
- Primate - monkey
- DOSE/DURATION :
- >1 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Administration onto the skin
- SPECIES OBSERVED :
- Rodent - rabbit
- DOSE/DURATION :
- 125 mg/kg
- TOXIC EFFECTS :
- Details of toxic effects not reported other than lethal dose value
- TYPE OF TEST :
- Specific locus test
- TYPE OF TEST :
- Cytogenetic analysis
- TYPE OF TEST :
- Cytogenetic analysis
MUTATION DATA - TYPE OF TEST :
- Sister chromatid exchange
- TEST SYSTEM :
- Rodent - hamster Ovary
- DOSE/DURATION :
- 310 ng/L
- REFERENCE :
- ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 36,1375,1986
- TYPE OF TEST :
- Sister chromatid exchange
- TEST SYSTEM :
- Rodent - hamster Ovary
- DOSE/DURATION :
- 310 ng/L
- REFERENCE :
- ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 36,1375,1986
Safety Information
| Symbol | GHS08 |
|---|---|
| Signal Word | Danger |
| Hazard Statements | H340-H360 |
| Precautionary Statements | P201-P280-P308 + P313 |
| Personal Protective Equipment | Eyeshields;full-face particle respirator type N100 (US);Gloves;respirator cartridge type N100 (US);type P1 (EN143) respirator filter;type P3 (EN 143) respirator cartridges |
| Hazard Codes | T: Toxic;T+: Very toxic; |
| Risk Phrases | R46;R61 |
| Safety Phrases | 53-36/37/39-45-22 |
| RIDADR | UN 3249 |
| WGK Germany | 3 |
| RTECS | CB5748500 |
| Packaging Group | III |
| Hazard Class | 6.1(b) |
| HS Code | 2914610000 |
Customs
| HS Code | 2914610000 |
|---|---|
| Summary | 2914610000 anthracene-9,10-dione。Supervision conditions:None。VAT:17.0%。Tax rebate rate:9.0%。Lowest tariff:5.5%。General tariff:30.0% |
Articles61
More Articles| Molecular mechanism of T-cell protein tyrosine phosphatase (TCPTP) activation by mitoxantrone. Biochim. Biophys. Acta 1834(10) , 1988-97, (2013) T-cell protein tyrosine phosphatase (TCPTP) is a ubiquitously expressed non-receptor protein tyrosine phosphatase. It is involved in the negative regulation of many cellular signaling pathways. Thus, ... | |
| Phase II trial assessing granulocyte-macrophage-colony stimulating factor, ketoconazole plus mitoxantrone in metastatic castration-resistant prostate cancer progressing after docetaxel treatments. Cancer Invest. 31(3) , 177-82, (2013) This study evaluated objective response and safety for the combination of granulocyte macrophage-colony stimulating factor (GM-CSF), ketoconazole, and mitoxantrone in castration-resistant prostate can... | |
| Sequential therapy with alternating short courses of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and R-FM (rituximab, fludarabine, mitoxantrone) followed by autologous stem cell transplantation results in long term remission in advanced follicular lymphoma. Br. J. Haematol. 166(4) , 625-8, (2014) |
Synonyms
| 1,4-dihydroxy-5,8-bis({2-[(2-hydroxyethyl)amino]ethyl}amino)anthracene-9,10-dione dihydrochloride |
| Mitoxantrone dihydrochloride |
| MITOXANTHRONE HYDROCHLORIDE |
| Mitoxantrone 2HCl |
| 1,4-dihydroxy-5,8-bis({2-[(2-hydroxyéthyl)amino]éthyl}amino)anthracène-9,10-dione dichlorhydrate |
| MITOZANTRONE |
| MFCD00242943 |
| 1,4-Dihydroxy-5,8-bis({2-[(2-hydroxyethyl)amino]ethyl}amino)anthracen-9,10-diondihydrochlorid |
| 1,4-dihydroxy-5,8-bis[2-(2-hydroxyethylamino)ethylamino]anthracene-9,10-dione,dihydrochloride |
| MITOXANTRONE HCl |
| 9,10-anthracenedione, 1,4-dihydroxy-5,8-bis[[2-[(2-hydroxyethyl)amino]ethyl]amino]-, dihydrochloride |
| Mitoxantrone hydrochloride |
| Novantron |
| Onkotrone |
| UNII-U6USW86RD0 |
| 1,4-Dihydroxy-5,8-bis[[2-[(2-hydroxyethyl)amino]ethyl]amino]-9,10-anthraquinone Dihydrochloride |
| EINECS 274-619-1 |
| 1,4-Dihydroxy-5,8-bis({2-[(2-hydroxyethyl)amino]ethyl}amino)-9,10-anthraquinone dihydrochloride |
| novatrone |
| 9,10-Anthracenedione, 1,4-dihydroxy-5,8-bis[[2-[(2-hydroxyethyl)amino]ethyl]amino]-, hydrochloride (1:2) |
| NSC-310739 |
| Mitoxantrone (dihydrochloride) |
